ORCID: Tamás Ágh,
This article was submitted to Drugs Outcomes Research and Policies, a section of the journal Frontiers in Pharmacology
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According to the estimation of the World Health Organization (WHO), adherence to long-term pharmacotherapies averages only 50% (
Several medication adherence enhancing interventions (MAEIs) - including many innovative technologies (e.g., smart devices, mobile applications) - have been developed in the last decade which may greatly improve suboptimal adherence to therapies and hence, therapeutic outcomes (
To our knowledge, there is a gap in the scientific literature with regards to the implementation, health technology assessment (HTA), policy regulation and reimbursement of MAEIs. In 2018, the Organisation for Economic Co-operation and Development (OECD) identified four enablers for improving medication adherence at the system level, such as (i) acknowledge (“to acknowledge that medication non-adherence harms health and increases healthcare costs”), (ii) inform (“to systematically monitor adherence”), (iii) incentivise (“to make changes in financial incentives for providers and patients”), and (iv) steer and support (“adherence begins with a patient and a prescribing clinician and a dispensing pharmacist who should all be supported by other health system stakeholders”) (
To overcome challenges related to implementing MAEIs, on October 2020 the European Network to Advance Best practices and technoLogy on medication adherencE (ENABLE, COST Action 19132) was launched. ENABLE is a 4-years research initiative funded by the European Commission that is expected to catalyze research, policy, and implementation regarding MAEIs across healthcare systems in all European countries and Israel (
An anonymous, web-based, cross-sectional survey, called the “EUropean REimbursement strategies for interventions targeting medication Adherence” (EUREcA), was performed across 38 European countries (i.e., Albania, Austria, Belgium, Bosnia and Herzegovina, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxemburg, Malta, Moldova, Montenegro, the Netherlands, North Macedonia, Norway, Poland, Portugal, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey, and the United Kingdom) and Israel. The target population of the survey was limited to members of ENABLE including academics with medical or pharmaceutical backgrounds, healthcare providers and health economists. Ethical issues for this study were governed by the Ethical Committee of the Medical University of Lodz, Poland. According to the policy of that Commission, non-experimental studies are not a subject to ethical approval procedure, and hence, such an approval was not needed. Each participant was requested to provide a written, online recorded informed consent before completing the survey. No personal data was stored in relation to this survey. The study was reported according to the Checklist for Reporting Results of Internet E-Surveys (CHERRIES) (
The primary outcome of the survey was a better understanding on the available reimbursed MAEIs across European countries. In relation to the aim of this study, MAEI was defined as “any structured intervention aiming to help patients to make optimal use of their pharmacotherapy”. Interventions of interest could be reimbursed/financed by public funds, pharma companies, patient organizations or any other organizations implemented at national and regional levels targeting any kind of pharmacotherapy (regardless of health condition). The survey questionnaire was developed as a result of an iterative process of discussion and consensus among the authors informed by a desk review. The draft questionnaire was validated by four external adherence experts with respect to the face validity and the technical functionality of the online questionnaire. Finally, the questionnaire contained one question on informed consent, three questions on demographic data, nine questions per intervention, allowing for maximum three reimbursed MAEIs per respondent per country, one question on data regarding reimbursed MAEIs planned to be introduced in the next 24 months and one question on any other relevant information. The majority of questions were closed, multiple-choice questions or “yes”/“no” questions; there were only two open-ended questions. A copy of the survey questionnaire can be seen in
The EUREcA survey was posted on
As the first step of data synthesis, a completeness check was conducted to ensure that adequate responses were received. Only data on interventions with complete set of information (i.e., answers were provided to all questions) were included in the analysis. In case of more than one respondent from a country, survey results were sent to the ENABLE country representatives for clarifications and data validation.
Data on the identified reimbursed MAEIs were presented in a descriptive way. Mann-Whitney
Fifty-four participants (survey response rate = 64%) covering all 39 ENABLE countries (1, 2, and three respondents from 26, 11, and two countries, respectively) completed the survey (
General characteristics of survey participants.
Country | Number of Survey Participants | Primary Field of Work (Work Experience in years) of Each Survey Participant |
---|---|---|
Albania | 1 | Academia (0–9 years) |
Austria | 1 | Clinical /Healthcare (10–19 years) |
Belgium | 1 | Commercial company /Industry (20–29 years) |
Bosnia and Herzegovina | 2 | Academia (10–19 years) |
Bulgaria | 2 | Academia (0–9 years) |
Croatia | 2 | Academia (10–19 years) |
Cyprus | 1 | Health Insurance /Regulatory Agency (20–29 years) |
Czech Republic | 1 | Academia (≥30 years) |
Denmark | 1 | Academia (20–29 years) |
Estonia | 2 | Health Insurance /Regulatory Agency (10–19 years) |
Finland | 1 | Academia (0–9 years) |
France | 1 | Commercial company /Industry (0–9 years) |
Germany | 1 | Academia (10–19 years) |
Greece | 1 | Academia (0–9 years) |
Hungary | 2 | Clinical /Healthcare (10–19 years) |
Iceland | 2 | Clinical /Healthcare (10–19 years) |
Ireland | 2 | Commercial company /Industry (0–9 years) |
Israel | 1 | Academia (0–9 years) |
Italy | 1 | Academia (10–19 years) |
Latvia | 1 | Clinical /Healthcare (20–29 years) |
Lithuania | 2 | Academia (20–29 years) |
Luxembourg | 1 | Academia (0–9 years) |
Malta | 1 | Academia (≥30 years) |
Moldova | 1 | Academia (10–19 years) |
Montenegro | 2 | Academia (20–29 years) |
Netherlands | 1 | Academia (10–19 years) |
North Macedonia | 1 | Academia (10–19 years) |
Norway | 1 | Academia (20–29 years) |
Poland | 1 | Academia (20–29 years) |
Portugal | 3 | Academia (≥30 years) |
Romania | 1 | Academia (20–29 years) |
Serbia | 1 | Academia (10–19 years) |
Slovakia | 1 | Academia (20–29 years) |
Slovenia | 1 | Clinical /Healthcare (20–29 years) |
Spain | 3 | Other: Research /Education not Academia (≥30 years) |
Sweden | 1 | Academia (20–29 years) |
Switzerland | 2 | Academia (≥30 years) |
Turkey | 1 | Academia (10–19 years) |
United Kingdom | 2 | Other: Clinical Academia (≥30 years) |
The survey identified 13 reimbursed MAEIs from nine countries (
Number of reimbursed medication adherence enhancing interventions across European countries.
Characteristics of identified reimbursed medication adherence enhancing interventions.
Type of Intervention | Country | Year of Introduction | Level of Intervention | Target Population | Who Pays the Reimbursement? | Who Gets the Reimbursement? |
---|---|---|---|---|---|---|
Multi-dose drug dispensing | Belgium | 2012 | National | Elderly patients | Public insurance /Public healthcare system /Government | Pharmacy |
Denmark | 2001 | National | Elderly patients | |||
Finland | 2006 | National | Reimbursed only for patients ≥75 years of age and using ≥6 drugs suitable for drug dispensing | |||
Norway | Early 2010s | National | Elderly patients | |||
United Kingdom | 2014 | National | Elderly patients, or those otherwise struggling to cope with their medication | |||
Medication review | Hungary | 2019 | National | 40–65 years old patients with chronic disorders | Public insurance /Public healthcare system /Government | Primary care (GP) |
Slovenia | 2016 | National | Patients with drug related problems; identified and referred by a GP | Primary care (clinical pharmacist) | ||
Spain | 2012 | Regional | Patients with chronic diseases and polypharmacy | Primary care, Hospital and Pharmacy | ||
United Kingdom | Years ago | National | Patients on long-term medication | Pharmacy and Hospital | ||
Smart device | Finland | 2019 | National | Patients on rheumatoid arthritis medication | Pharma company | IT company |
Netherlands | 2020 | National | Patients with asthma/COPD | Public insurance /Public healthcare system /Government and Pharma company | Pharmacy | |
Mobile application | Denmark | No information | National | Patients with mental disorder | No information | No information |
Patient education | Hungary | 2016 | National | Newly transplanted patients | Patient organization | Healthcare providers |
COPD, chronic obstructive pulmonary disease; GP, general practitioner; IT, information technology.
MDD services were implemented and reimbursed primarily in Northern and Western European countries (i.e., Belgium, Denmark, Finland, Norway, and the United Kingdom). In all countries MDD services were reimbursed by public health insurance predominantly to older people who take multiple medicines either at home or in nursing homes.
Based on our results, medication review was reimbursed in 4 European countries (i.e., Hungary, Slovenia, Spain, and the United Kingdom). In all but one of these countries this service was provided by primary care centers; in the United Kingdom community pharmacies were responsible for medication review. The identified medication review services were reimbursed by public health insurance primarily for patients with chronic disorders. In Slovenia, two types of medication reviews were available. The “type 3” medication review (
Experts from Finland and the Netherlands reported that in their countries there were reimbursed adherence enhancing smart devices. Popit Sense® is a smart device for monitoring pill-taking. The device monitors through sensors when pills are taken. Data on pill consumption are sent to Popit Pill Reminder Application® on a smartphone. This smart device was reimbursed by a pharma company in Finland for patients with rheumatoid arthritis. Another example is the Enerzair® smart inhaler which is a drug-device combination (devices integrated with a drug and dispensed at the same time). The device is connected with a mobile application for self-monitoring. This smart inhaler was reimbursed by the national health insurance in the Netherlands for the maintenance treatment of asthma/COPD in adult patients.
In our survey we identified only one reimbursed mobile health application for enhancing medication adherence. MindFrame® is a mobile health solution that supports the treatment of individuals suffering from schizophrenia in Denmark. This application helps patients to play a more active role in their treatment and allows mental health professionals to monitor patients remotely.
Last but not least, we identified one reimbursed patient education program as well. The “Be Educated and Empowered Patient” (BEEP) is an education program for organ transplanted patients launched by the Hungarian Transplant Federation. The program was reimbursed from various funds of pharma companies and state grants. This program primarily aims to improve the health literacy level and health behaviour of newly transplanted patients and thus it only has an indirect effect on medication adherence.
We found a significant difference between the median real GDP per capita (
Association between country income and health care expenditure, and the availability of reimbursed medication adherence enhancing interventions across European countries. GDP: gross domestic product; MAEI: medication adherence enhancing intervention.
To our knowledge, this is the first study to provide an in-depth overview on reimbursed MAEIs across Europe. From the evaluated 39 countries, there were only nine countries in which we could identify reimbursed adherence interventions. Our findings confirm that despite of the considerable economic and clinical burdens of medication non-adherence, MAEIs remain on a low priority on the health policy agenda of funding bodies. In the European Union, almost 200,000 people die each year because of non-adherence and the direct and indirect costs of poor adherence were estimated to be 80–125 billion EUR annually (
At present, there is no uniform terminology for MAEIs which made it difficult to identify reimbursed adherence interventions. In our survey, MAEI was defined by the authors as a result of discussion and consensus as “any structured intervention aiming to help patients to make optimal use of their pharmacotherapy”. However, it might be that respondents interpreted this definition differently when determining whether an intervention affects medication adherence or not. One uniform, common accepted, standard definition for MAEI would be highly warranted to be able to define interventions improving adherence more precisely; particularly in the view of the wide range of various types of educational (e.g., group/individual education provided by physicians, pharmacists, nurses, allied health professionals) and behavioural (e.g., calendar/diary, reminder chart/medication list, large print labels, packaging change, multi-compartment pillbox/calendar pack/compliance aid, adherence monitoring, reminders) interventions developed recently (
In total, 13 reimbursed MAEIs were included in our analysis from which MDD and medication review were the most common. In general, as part of MDD, medicines such as tablets, capsules and pills are repackaged with a special equipment automatically into unit-dose bags according to the time of administration, then these bags are dispensed by the community pharmacy to the patient. Unit-dose bags are labelled with the patient’s identification data, the drug name, and time of administration (
Other types of MAEIs such as e-health technologies (e.g., smart devices, mobile applications) or patient education programs were reimbursed only in limited number of European countries. Nevertheless, several e-health interventions have been developed in the past few years (
Based on these findings we can conclude that although several studies have demonstrated that MAEIs may improve clinical outcomes (
The majority (77%) of the identified MAEIs were reimbursed from public health care funds; however, improving medication adherence is a common goal of all stakeholders in the health care system (i.e., policy makers, pharma industry, health care providers, pharmacists, patients and caregivers). A close cooperation of key stakeholders related to the reimbursement of MAEIs could add a surplus value to the implementation by bridging the gap between clinical research and clinical practice.
We found a statistically significant association between country income (i.e., real GDP per capita,
Our results should be considered in the light of certain limitations. First, participants’ answers to the survey may be biased by their subjectivity, background and work experience. The survey was completed by ENABLE members and in some countries, information was based on the answers of only one participant. The majority of respondents had academic background (i.e., medical or pharmaceutical sciences) and they might not have sufficient information on e.g. specific MAEIs reimbursed by pharma companies to patients with certain diseases only. Furthermore, it should be noted that the lack of a common definition for MAEIs might also bias the identification of reimbursed interventions. Although our survey might not provide a complete picture on the reimbursement landscape of MAEIs in Europe, it does provide a useful starting point for discussion and may also help to determine where further research is needed. Finally, our survey questionnaire with many closed questions allowed us to capture very specific information on MAEIs. To minimize the potential risks of the self-developed questionnaire, external experts were asked to assess its validity and technical functionality.
In conclusion, to date only a small number of MAEIs have been reimbursed across Europe. Discussions about MAEIs is hampered by the lack of a common terminology. Besides the clinical studies, more research effort should be devoted to better understand the effect of MAEIs on economic outcomes. Specific HTA process guidelines involving multiple value indicators and consequently the comprehensive assessment of MAEIs would help to identify the most effective and cost-effective adherence programs. A close cooperation of key stakeholders related to the reimbursement of MAEIs could set new benchmark to manage medication non-adherence.
Sarah Wamala Andersson, Manon Belhassen, Katharina Blankart, Martina Bago, Job F. M. van Boven, Dragana Drakul, Natasa Duborija-Kovacevic, Lallas Efthymios, Dalma Erdősi, Nuria Garcia-Agua Soler, Bettina Husebo, Ivett Jakab, Barbora Kostalova, Jesper Kjærgaard, Dusanka Krajnovic, Fatjona Kamberi, Ott Laius, Francisca Leiva-Fernandez, Urska Nabergoj Makovec, Paulo Moreira, Zornitsa Mitkova, Panayiotis Petrou, Mitar Popovic, Marie Paule Schneider Voirol, Vesna Vujic-Aleksic, Bruno Velescu, Daisy Volmer, and Martin Wawruch
The raw data supporting the conclusion of this article will be made available by the authors, without undue reservation.
All authors contributed to conception and design of the study. TA, MH, KG and PK developed the first draft of the survey questionnaire. TA and PK aggregated responses to the survey and organized the database. TA performed the statistical analysis. TA wrote the first draft of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.
This research is based upon work from COST Action CA19132 “ENABLE,” funded by COST (European Cooperation in Science and Technology). The funder had no role in the study design, data collection, analysis and interpretation, or preparation of the manuscript.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Authors would like to express their gratitude to Elizabeth Manias, Donald Morisky, Andrew M. Peterson and Adina Turcu for their support in the validation process of the survey questionnaire.
The Supplementary Material for this article can be found online at: